What question did this study set out to answer?

To develop a carboxymethyl cellulose hydrogel that extends the half-life of recombinant IL-22 for improved treatment of alcoholic liver disease.

April 8, 2026Open Access

Injectable pH-responsive carboxymethyl cellulose hydrogel for sustained delivery of IL-22 in the treatment of alcoholic liver disease

Key Points

To develop a carboxymethyl cellulose hydrogel that extends the half-life of recombinant IL-22 for improved treatment of alcoholic liver disease.
Developed a carboxymethyl cellulose hydrogel encapsulated with recombinant interleukin-22
Utilized hydrogen bonding interactions for drug incorporation
Assessed biocompatibility and pH-responsive drug delivery properties
Evaluated therapeutic efficacy through alanine aminotransferase and aspartate aminotransferase level measurement
Conducted RNA sequencing to analyze signaling pathway involvement.
IL-22@CMC reduced ALT levels from 250 IU/L to 100 IU/L
IL-22@CMC reduced AST levels from 700 IU/L to 200 IU/L
Both ALT and AST levels were significantly lower compared to IL-22 alone
Enhanced inhibitory effect was linked to reduced endoplasmic reticulum stress via signaling pathway modulation.

Abstract

Alcoholic liver disease (ALD) is a major chronic liver disorder that poses a significant global health burden due to its severe health risks and limited therapeutic options. Although recombinant interleukin-22 (IL-22) is an available therapeutic agent with potent anti-inflammatory and anti-lipid accumulation effects, its application in ALD treatment has been limited by its short half-life. In this study, we developed a carboxymethyl cellulose hydrogel (CMC)-encapsulated system to prolong the half-life of recombinant IL-22, aiming to achieve effective and sustained inhibition of ALD. Recombinant IL-22 was incorporated into CMC (IL-22@CMC) through hydrogen bonding interactions. This system exhibited pH-responsive drug delivery properties and good biocompatibility. IL-22@CMC reduced alanine aminotransferase (ALT) levels from 250 IU/L to 100 IU/L and aspartate aminotransferase (AST) levels from 700 IU/L to 200 IU/L. These levels were significantly lower than those observed with IL-22 alone (160 IU/L and 400 IU/L, respectively), indicating superior therapeutic efficacy in alcoholic liver injury. RNA sequencing analysis indicated that the enhanced inhibitory effect of IL-22@CMC was achieved through suppression of endoplasmic reticulum stress mediated by the AMP-activated protein kinase/sirtuin 1 signaling pathway in ethanol-induced AML-12 cells. By designing a pH-responsive hydrogel, this study integrates therapeutic agents with a hydrogel carrier via hydrogen bonding, thereby providing an effective strategy for developing drug delivery composites for inflammatory diseases.

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Cite This Study

Zhou et al. (Mon,) studied this question.

synapsesocial.com/papers/69d5efd374eaea4b11a79696 https://doi.org/https://doi.org/10.1186/s12951-026-04345-x

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